Osimertinib has been reported to be effective against central nervous system (CNS) metastasis from activating EGFR mutation-positive NSCLC. Nevertheless, the true antitumor effects of osimertinib alone for CNS metastasis are unclear because the aforementioned studies included previously irradiated cases, in which tumor shrinkage can occur later owing to the effects of radiotherapy (RT). This study aimed to evaluate the efficacy of osimertinib against RT-naive CNS metastasis from sensitizing EGFR mutation-positive NSCLC. The OCEAN study was a two-cohort trial, involving 66 patients (T790M cohort [n = 40] and first-line cohort [n = 26]) with RT-naive CNS metastasis from sensitizing EGFR mutation-positive NSCLC. The patients were treated once daily with 80 mg osimertinib. The primary end point was brain metastasis response rate (BMRR) according to the PAREXEL criteria. In this report, we present the results for the T790M cohort with analysis of drug concentrations and plasma circulating tumor DNA. The median age of the patients was 69 years, and 30% of them were males. Eight patients (20%) were symptomatic, and most had multiple CNS metastases (78%). Among the eligible 39 patients, the BMRR (PAREXEL criteria), median brain metastasis-related progression-free survival (PFS), median overall survival, overall response rate, and median PFS were 66.7% (90% confidence interval: 54.3%-79.1%), 25.2 months, 19.8 months, 40.5%, and 7.1 months, respectively. The BMRR according to the Response Evaluation Criteria in Solid Tumors criteria was 70.0% (n = 20). The brain metastasis-related PFS of patients with EGFR exon 19 deletion was significantly longer than that of exon 21 L858R (median = 31.8 versus 8.3 mo; log-rank p = 0.032). The treatment-related pneumonitis was observed in four patients (10%). On or after day 22, the median trough blood and cerebrospinal fluid concentrations of osimertinib were 568 nM and 4.10 nM, respectively, and those of its metabolite AZ5104 were 68.0 nM and 0.260 nM, respectively. The median blood to cerebrospinal fluid penetration rates of osimertinib and AZ5104 were 0.79% and 0.53%, respectively. The blood trough concentration at day 22 was not correlated with the efficacy of osimertinib against CNS metastasis. Plasma T790M and C797S mutations were detected in 83% and 3% of the patients before treatment, 11% and 3% of the patients on day 22, and 39% and 22% of the patients at the detection of progressive disease, respectively. This study evaluated the efficacy of osimertinib against RT-naive CNS metastasis from T790M-positive NSCLC. The primary end point was met, and the results revealed the efficacy of osimertinib in patients with CNS metastasis harboring EGFR T790M mutations especially for EGFR-sensitizing mutation of exon 19 deletion.

To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial. Eligibility criteria were: chemotherapy-naïve, small-cell lung cancer (SCLC), good performance status (PS: 0–2), age75 years, and adequate organ function. The patients' characteristics were: male/female=56/5; PS 0/1/2=19/38/4; median age (range)=68 years(51–75 years); limited disease (LD)/extensive disease (ED)=27/34. The patients received irinotecan (50 mg m⁻²) on days 1, 8, and 15, and carboplatin (AUC 5, Chatelut formula) on day 1 every 4 weeks. In total, 61 patients were eligible and all were evaluated. In all, 31 patients were treated with four or more courses of chemotherapy. Of the patients, 17 showed a complete response (CR), 34 showed a partial response (PR), nine had stable disease (SD), and one had progressive disease (PD). The overall response rate was 84% (95% confidence interval (CI), 72–91%; LD 89%, ED 79%) and the CR rate was 28% (95%CI, 17–41%; LD 37%, ED 21%). The median time to tumour progression was 6.1 (LD 6.4, ED 5.4) months. The medial survival time was 15.0 (LD 20.0, ED 9.7) months, and the 2-year and 5-year survival rates were 31.1% (LD 48.1%, ED 17.7%) and 9.5% (LD 11.1%, ED 5.9%), respectively. Grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, anaemia, and diarrhoea occurred in 33, 74, 41, 39, and 13% of cases, respectively. In conclusion, the combination of irinotecan and carboplatin is an active and well-tolerated regimen in cases of SCLC.

Pulmonary pleomorphic carcinoma has been shown to respond remarkably to PD‐1 inhibitors; however, the biomarkers for this therapy have not been fully proven. We report a case of pulmonary pleomorphic carcinoma with overexpressed PD‐L1, in which a complete response to nivolumab was sustained for >14 months. Immunohistochemical analysis revealed few PD‐1⁺ immune cells and regulatory T cells in the tumor, in addition to predominant infiltration of CD8⁺ cells and macrophages. Our findings suggest that the presence of a small number of PD‐1⁺ immune cells and regulatory T cells should be investigated as candidate therapeutic biomarkers.

Background: The study was conducted to evaluate the clinical and computed tomography (CT) findings of non‐small cell lung cancer (NSCLC) patients to distinguish between ALK gene rearrangement, EGFR mutation, and non‐ ALK / EGFR (no genetic abnormalities). Methods: We enrolled 201 patients with primary NSCLC who had undergone molecular testing for both ALK gene rearrangement and EGFR mutation. The clinical features and CT findings of the main lesion and associated pulmonary abnormalities were investigated. Results: Female gender ( P = 0.0043 vs. non‐ ALK / EGFR ), young age ( P = 0.0156 vs. EGFR ), and a light or never smoking history ( P = 0.0039 vs. non‐ ALK / EGFR ) were significant clinical characteristics of NSCLC with ALK gene rearrangement. The significant CT characteristics compared to NSCLC with EGFR mutation were a large mass ( P = 0.0155), solid mass ( P = 0.0048), and no air bronchogram ( P = 0.0148). A central location ( P = 0.0322) and lymphadenopathy ( P = 0.0353) were also more frequently observed. Coexisting emphysema was significantly less frequent in NSCLC patients with ALK gene rearrangement ( P = 0.0135) than non‐ ALK / EGFR . Conclusions: NSCLC with ALK gene rearrangement was more likely to develop in younger women with a light or never smoking history. The characteristic CT findings of NSCLC with ALK gene rearrangement were a large solid mass, less air bronchogram, a central location, and lymphadenopathy.

Purpose: This study aimed to evaluate the clinical courses of patients with surgically resected stage IA pulmonary adenocarcinoma (Ad) who exhibited heterogeneous ground-glass nodules (GGNs) or part-solid nodules on thin-section computed tomography (TSCT) and to clarify the prognostic differences between them. Materials and methods: The cases of 242 patients with proven pulmonary Ad with heterogeneous GGN or part-solid nodule who underwent surgical resection were retrospectively reviewed. After surgery, they were examined pathologically. Disease-free survival (DFS) and overall survival (OS) were also investigated. Results: There were no cases of recurrent pulmonary Ad or death from the primary disease in the heterogeneous GGN group. In the part-solid nodule group, recurrent pulmonary Ad and death from the primary disease were observed in 12 and 6 of 181 patients, respectively. Heterogeneous GGNs were associated with significantly longer DFS than part-solid nodules (p = 0.042). While, there was no significant difference in OS between the two groups (p = 0.134). Pathological diagnoses were available for all 242 patients. 181 part-solid nodules were classified into 116 invasive Ads, 54 minimally invasive Ads (MIAs), and 11 Ad in situ (AIS) lesions, and 61 heterogeneous GGNs were classified into 18 invasive Ads, 25 MIAs, and 18 AIS lesions. Conclusion: Heterogeneous GGNs were significantly associated with longer DFS than part-solid nodules. Pathologically, there were significant differences between the heterogeneous GGNs and part-solid nodules.